DESCRIPTION: Oral cavity cancer is the 6th most common cancer in the United States. Pathogenesis of this cancer includes specific features of histopathological and molecular progression from normal to premalignant to tumor. Yet the molecular basis of this solid tumor is not well understood. Only 18 percent of oral premalignancies progress to cancer. The ability to predict the malignant progression of oral premalignancies will reduce the mortality and restricts the morbidity of this cancer since it is readily accessible for examination. This Exploratory Project is a sequential series of studies to test the hypothesis that broad gene expression monitoring using high-density microarrays offers the potential to identify genes in the malignant progression of oral premalignancies. Three Specific Aims are in place to test this hypothesis. Specific Aim 1 is to obtain gene expression profiles for 12,000 genes on progressing and non-progressing human oral premalignancies. Specific Aim 2 is to use bioinformatics tools to generate an "Oral Premalignancy Progression Predictor Gene" set (OPPPG). Specific Aim 3 is to validate the OPPPG set on an independent sample set. The proposed work is based on a history of successful collaborations amongst the investigators who are at the forefront of the respective fields. The outcome of this application will be unique and highly relevant molecular resources capable of predicting of oral premalignancy progression. In addition to understanding the biology and pathogenesis of this cancer, the generated results will serve as basis of future clinical and translational applications such as diagnostics, molecular epidemiology and treatment outcome monitoring of oral cancer patients (R33 and RO1).